The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TP53BP1  -  tumor protein p53 binding protein 1

Homo sapiens

Synonyms: 53BP1, Tumor suppressor p53-binding protein 1, p202, p53-binding protein 1, p53BP1
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TP53BP1


High impact information on TP53BP1


Chemical compound and disease context of TP53BP1


Biological context of TP53BP1

  • Here, we report that 53BP1 becomes hyperphosphorylated and forms discrete nuclear foci in response to DNA damage [2].
  • The LC8-binding domain was mapped to a short peptide segment immediately N-terminal to the kinetochore localization region of 53BP1 [11].
  • 53BP1 is required for at least a subset of ataxia telangiectasia-mutated (ATM)-dependent phosphorylation events at sites of DNA breaks and for cell cycle arrest at the G2-M interphase after exposure to irradiation [12].
  • This checkpoint protects against apoptosis because depletion of 53BP1 or p21(WAF1/CIP1) increases both the rate and extent of apoptosis [13].
  • E2F1-induced MRN foci are similar to irradiation-induced foci (IRIF) that result from double-strand DNA breaks because they correlate with 53BP1 and gammaH2AX foci, do not form in NBS cells, do form in AT cells and do not correlate with cell cycle entry [13].

Anatomical context of TP53BP1

  • Fibroblast cells treated with methylase inhibitors failed to relocalize 53BP1 to sites of DNA damage and formed few gamma-H2AX foci, consistent with our previous data that MRE11 fails to relocalize to DNA damage sites in cells treated with methylase inhibitors [14].
  • Silencing of HDAC4 via RNA interference surprisingly also decreased levels of 53BP1 protein, abrogated the DNA damage-induced G2 delay, and radiosensitized HeLa cells [15].
  • Enhanced intra-switch region recombination during immunoglobulin class switch recombination in 53BP1(-/-) B cells [16].
  • Microwaves from GSM mobile telephones affect 53BP1 and gamma-H2AX foci in human lymphocytes from hypersensitive and healthy persons [17].
  • The expression of the MDM2 gene, a p53 binding protein, in thyroid carcinogenesis [18].

Associations of TP53BP1 with chemical compounds


Physical interactions of TP53BP1

  • The interaction is augmented in a phospho-dependent manner, and the MDC1 binding region of 53BP1 is phosphorylated in vivo in mitotic cells; therefore, it is probably modulated by cell cycle-regulated kinases [22].

Enzymatic interactions of TP53BP1

  • Third, 53BP1 is readily phosphorylated by ATM in vitro [2].
  • Like many proteins involved in the DNA damage response, 53BP1 becomes hyperphosphorylated after radiation and colocalizes with phosphorylated H2AX in megabase regions surrounding the sites of DNA strand breaks [23].

Co-localisations of TP53BP1


Regulatory relationships of TP53BP1


Other interactions of TP53BP1

  • Taken together, these results suggest that 53BP1 is an ATM substrate that is involved early in the DNA damage-signaling pathways in mammalian cells [2].
  • Unlike other known LC8-binding proteins, 53BP1 contains two distinct LC8-binding motifs that are arranged in tandem [11].
  • Therefore, 53BP1 can potentially act as an adaptor to assemble p53 to the dynein complex [11].
  • Whether 53BP1 and NFBD1 are required for activation of kinases and/or for recruitment of substrates at IRIF, however, is not clear [27].
  • However, it is not known whether E2F1-mediated apoptosis can be counteracted by p202 expression [4].
  • Our data suggest that TP53BP1 variants may have protective effects on SCCHN risk but such effects were confined to TP53 variant allele/haplotype carriers [28].

Analytical, diagnostic and therapeutic context of TP53BP1


  1. p53-Binding protein 1 is fused to the platelet-derived growth factor receptor beta in a patient with a t(5;15)(q33;q22) and an imatinib-responsive eosinophilic myeloproliferative disorder. Grand, F.H., Burgstaller, S., Kühr, T., Baxter, E.J., Webersinke, G., Thaler, J., Chase, A.J., Cross, N.C. Cancer Res. (2004) [Pubmed]
  2. Tumor suppressor p53 binding protein 1 (53BP1) is involved in DNA damage-signaling pathways. Rappold, I., Iwabuchi, K., Date, T., Chen, J. J. Cell Biol. (2001) [Pubmed]
  3. p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. Schultz, L.B., Chehab, N.H., Malikzay, A., Halazonetis, T.D. J. Cell Biol. (2000) [Pubmed]
  4. P202, an interferon-inducible protein, inhibits E2F1-mediated apoptosis in prostate cancer cells. Yan, D.H., Abramian, A., Li, Z., Ding, Y., Wen, Y., Liu, T.J., Hunt, K. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  5. A role for the deubiquitinating enzyme USP28 in control of the DNA-damage response. Zhang, D., Zaugg, K., Mak, T.W., Elledge, S.J. Cell (2006) [Pubmed]
  6. Structural Basis for the Methylation State-Specific Recognition of Histone H4-K20 by 53BP1 and Crb2 in DNA Repair. Botuyan, M.V., Lee, J., Ward, I.M., Kim, J.E., Thompson, J.R., Chen, J., Mer, G. Cell (2006) [Pubmed]
  7. MDC1 accelerates nonhomologous end-joining of dysfunctional telomeres. Dimitrova, N., de Lange, T. Genes Dev. (2006) [Pubmed]
  8. Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure. Joo, W.S., Jeffrey, P.D., Cantor, S.B., Finnin, M.S., Livingston, D.M., Pavletich, N.P. Genes Dev. (2002) [Pubmed]
  9. TP53-binding protein variants and breast cancer risk: a case-control study. Frank, B., Hemminki, K., Bermejo, J.L., Klaes, R., Bugert, P., Wappenschmidt, B., Schmutzler, R.K., Burwinkel, B. Breast Cancer Res. (2005) [Pubmed]
  10. Prostate-specific antitumor activity by probasin promoter-directed p202 expression. Wen, Y., Giri, D., Yan, D.H., Spohn, B., Zinner, R.G., Xia, W., Thompson, T.C., Matusik, R.J., Hung, M.C. Mol. Carcinog. (2003) [Pubmed]
  11. The 8-kDa dynein light chain binds to p53-binding protein 1 and mediates DNA damage-induced p53 nuclear accumulation. Lo, K.W., Kan, H.M., Chan, L.N., Xu, W.G., Wang, K.P., Wu, Z., Sheng, M., Zhang, M. J. Biol. Chem. (2005) [Pubmed]
  12. 53BP1 functions in an ATM-dependent checkpoint pathway that is constitutively activated in human cancer. DiTullio, R.A., Mochan, T.A., Venere, M., Bartkova, J., Sehested, M., Bartek, J., Halazonetis, T.D. Nat. Cell Biol. (2002) [Pubmed]
  13. E2F1 induces MRN foci formation and a cell cycle checkpoint response in human fibroblasts. Frame, F.M., Rogoff, H.A., Pickering, M.T., Cress, W.D., Kowalik, T.F. Oncogene (2006) [Pubmed]
  14. The GAR motif of 53BP1 is arginine methylated by PRMT1 and is necessary for 53BP1 DNA binding activity. Boisvert, F.M., Rhie, A., Richard, S., Doherty, A.J. Cell Cycle (2005) [Pubmed]
  15. Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response. Kao, G.D., McKenna, W.G., Guenther, M.G., Muschel, R.J., Lazar, M.A., Yen, T.J. J. Cell Biol. (2003) [Pubmed]
  16. Enhanced intra-switch region recombination during immunoglobulin class switch recombination in 53BP1(-/-) B cells. Reina-San-Martin, B., Chen, J., Nussenzweig, A., Nussenzweig, M.C. Eur. J. Immunol. (2007) [Pubmed]
  17. Microwaves from GSM mobile telephones affect 53BP1 and gamma-H2AX foci in human lymphocytes from hypersensitive and healthy persons. Markovà, E., Hillert, L., Malmgren, L., Persson, B.R., Belyaev, I.Y. Environ. Health Perspect. (2005) [Pubmed]
  18. The expression of the MDM2 gene, a p53 binding protein, in thyroid carcinogenesis. Zou, M., Shi, Y., al-Sedairy, S., Hussain, S.S., Farid, N.R. Cancer (1995) [Pubmed]
  19. p202, an interferon-inducible modulator of transcription, inhibits transcriptional activation by the p53 tumor suppressor protein, and a segment from the p53-binding protein 1 that binds to p202 overcomes this inhibition. Datta, B., Li, B., Choubey, D., Nallur, G., Lengyel, P. J. Biol. Chem. (1996) [Pubmed]
  20. Jun activation domain-binding protein 1 is required for mitotic checkpoint activation via its involvement in hyperphosphorylation of 53BP1. Kwak, H.J., Kim, S.H., Yoo, H.G., Park, S.H., Lee, C.H. J. Cancer Res. Clin. Oncol. (2005) [Pubmed]
  21. Distinct residues of human p53 implicated in binding to DNA, simian virus 40 large T antigen, 53BP1, and 53BP2. Thukral, S.K., Blain, G.C., Chang, K.K., Fields, S. Mol. Cell. Biol. (1994) [Pubmed]
  22. The direct interaction between 53BP1 and MDC1 is required for the recruitment of 53BP1 to sites of damage. Eliezer, Y., Argaman, L., Rhie, A., Doherty, A.J., Goldberg, M. J. Biol. Chem. (2009) [Pubmed]
  23. Accumulation of checkpoint protein 53BP1 at DNA breaks involves its binding to phosphorylated histone H2AX. Ward, I.M., Minn, K., Jorda, K.G., Chen, J. J. Biol. Chem. (2003) [Pubmed]
  24. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Chan, D.W., Chen, B.P., Prithivirajsingh, S., Kurimasa, A., Story, M.D., Qin, J., Chen, D.J. Genes Dev. (2002) [Pubmed]
  25. Inhibition of E2F-4/DP-1-stimulated transcription by p202. Choubey, D., Gutterman, J.U. Oncogene (1997) [Pubmed]
  26. The MCT-1 oncogene product impairs cell cycle checkpoint control and transforms human mammary epithelial cells. Hsu, H.L., Shi, B., Gartenhaus, R.B. Oncogene (2005) [Pubmed]
  27. NFBD1/Mdc1 mediates ATR-dependent DNA damage response. Peng, A., Chen, P.L. Cancer Res. (2005) [Pubmed]
  28. Polymorphic TP53BP1 and TP53 gene interactions associated with risk of squamous cell carcinoma of the head and neck. Chen, K., Hu, Z., Wang, L.E., Zhang, W., El-Naggar, A.K., Sturgis, E.M., Wei, Q. Clin. Cancer Res. (2007) [Pubmed]
  29. hSnm1 colocalizes and physically associates with 53BP1 before and after DNA damage. Richie, C.T., Peterson, C., Lu, T., Hittelman, W.N., Carpenter, P.B., Legerski, R.J. Mol. Cell. Biol. (2002) [Pubmed]
  30. NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage. Peng, A., Chen, P.L. J. Biol. Chem. (2003) [Pubmed]
  31. Purification, crystallization and preliminary X-ray analysis of the BRCT domains of human 53BP1 bound to the p53 tumour suppressor. Derbyshire, D.J., Basu, B.P., Date, T., Iwabuchi, K., Doherty, A.J. Acta Crystallogr. D Biol. Crystallogr. (2002) [Pubmed]
WikiGenes - Universities